日志
以色列报告 COVID-19 疫苗引起心脏炎
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以色列报告 COVID-19 疫苗引起心脏炎
以色列报告称，年轻男性罕见的心脏炎症病例与 COVID-19 疫苗接种之间存在联系 研究加强了 4 月首次公布的怀疑，但大多数病例都是轻微的
2021 年 6 月 1 日，作者：GRETCHEN VOGEL、JENNIFER COUZIN-FRANKEL
科学的 COVID-19 报告得到了 Heising-Simons 基金会的支持。
以色列研究人员表示，辉瑞和 BioNTech 生产的 COVID-19 疫苗似乎使年轻男性患上心肌炎症（称为心肌炎）的风险增加。在今天提交给以色列卫生部的一份报告中，他们得出结论，接种疫苗的 16 至 24 岁男性中，每 3000 到 6000 人中就有 1 人患上这种罕见疾病。但大多数病例都是轻微的，并在几周内得到解决，这是心肌炎的典型症状。 “我无法想象医务人员会因为什么原因说我们不应该给孩子接种疫苗，”西雅图儿童医院的儿科医生兼生物伦理学家道格拉斯·迪克马 (Douglas Diekema) 说。
以色列卫生官员于 4 月首次提出这一问题，当时他们报告了 60 多例病例，其中大部分是几天前接种了第二剂疫苗的年轻男性。大约在同一时间，美国国防部开始追踪 14 例此类病例。5 月中旬，美国疾病控制和预防中心表示，它也在审查心肌炎病例。欧洲药品管理局的官员于 5 月 28 日表示，他们收到了 107 份辉瑞-BioNTech 疫苗接种后心肌炎的报告，大约每 175,000 剂疫苗中就有 1 例。但在欧洲，接种疫苗的 30 岁以下人群相对较少。
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以色列专家组得出这一结论之际，以色列和许多欧洲国家正在争论是否应该为年龄较小的青少年接种 COVID-19 疫苗。以色列自 1 月底以来一直在为 16 岁及以上的青少年接种疫苗，卫生部定于明天宣布是否向 12 岁及以上的儿童开放疫苗接种。包括美国和加拿大在内的其他国家已于 5 月中旬开始为 12 岁及以上的儿童接种疫苗。
“从父母的角度来看，这实际上取决于风险认知和数据评估，”研究风险收益权衡的 Diekema 说。即使心肌炎和疫苗之间存在联系，病情通常也很轻微，只需要用消炎药治疗，而 COVID-19 感染也会导致严重疾病和长期副作用，即使在年轻人中也是如此。随着人们对可能存在的联系产生怀疑，“我所知道的医生中，没有多少人会改变主意，不给孩子接种疫苗，”迪克马说。
在以色列，早期的快速疫苗接种运动几乎完全依赖辉瑞-BioNTech 疫苗，卫生部于 1 月组建了一个由哈达萨大学医学中心内科主任 Dror Mevorach 领导的小组，调查这一问题。Mevorach 告诉《科学》杂志，他和他的同事在确诊前一个月接种了两剂辉瑞-BioNTech 疫苗的 500 万人中发现了 110 例心肌炎病例。这意味着每 50,000 名疫苗接种者中就有 1 人患上心肌炎，这个数字并不令人担忧，因为普通人群中心肌炎的发病率通常由病毒或细菌感染引发，包括 COVID-19。
但年轻男性接种疫苗后心肌炎的发病率更高。报告称，以色列发现的 90% 病例发生在男性身上，尽管心肌炎在年轻男性中更常见，但接种疫苗的人的发病率是背景发病率的 5 到 25 倍。（以色列还报告了两例致命的心肌炎病例，但专家组表示，对这些死亡病例的调查尚无定论；一名患者可能患有更普遍的炎症综合症，另一名患者的诊断“未经证实”。）
Mevorach 说，新的分析“非常暗示疫苗和心肌炎之间存在因果关系”。 “我确信两者之间存在某种关系。”
“这确实表明，至少从统计学上讲，这是一种真实现象，”渥太华大学心脏研究所的心脏病专家兼首席科学官 Peter Liu 说。Diekema 说，调查“哪怕是一点点信号”都很重要，但他警告说，“虽然这份报告很有启发性……但需要其他研究人员在其他人群中验证，才能确定存在这种联系。”迪克马说，其他因素可能也起到了作用。现在孩子们又开始社交和运动了，他所在医院的急诊室“发现的病毒性疾病比一年前还多”，因此，“我预计心肌炎发病率会比一年前略有上升。”理想情况下，科学家应该比较接种疫苗和未接种疫苗的人群
迪克马说，他很高兴看到此类研究正在加速进行。
以色列尚未使用 Moderna 疫苗，但美国也在调查接种该疫苗后出现的心肌炎病例。目前尚不清楚这两种疫苗为何会增加风险，这两种疫苗都依赖于信使 RNA (mRNA)。一种可能性是，这两种疫苗在年轻人体内产生的极高抗体水平，在极少数情况下，也可能导致一种免疫过度反应，从而引起心脏炎症。刘说：“毫无疑问，这些 [疫苗] 具有极强的免疫力。”梅沃拉赫说，他怀疑 mRNA 本身可能发挥了作用。他指出，先天免疫系统将 RNA 识别为人体防御微生物（包括 SARS-CoV-2 等 RNA 病毒）的一部分。他说：“我认为 mRNA 实际上是一种天然佐剂”，可以增强免疫反应。
迪克马表示，医学界现在对接种疫苗后不久出现胸痛和其他症状的年轻人保持警惕——以便迅速发现、治疗并向卫生部门报告。梅沃拉奇同意，接种疫苗者、他们的父母和医生的意识对于及时有效的治疗非常重要。他说，他和他的同事治疗了大约 40 例病例。他说，只有少数人需要皮质类固醇，大多数人已经完全康复。
一个重要的问题是，推迟第二剂疫苗接种是否可以降低任何潜在风险。也许有机会找出答案：几个国家将两剂疫苗的间隔时间从辉瑞测试和推荐的 3 周延长到 12 周甚至 16 周，因为他们希望让尽可能多的人至少接种一剂。第二剂疫苗接种延迟的人心肌炎病例的下降可能会在未来几个月的数据中体现出来。刘说，降低年轻人的剂量也可能值得考虑。辉瑞和 Moderna 的疫苗目前正在 12 岁以下儿童中以较低剂量进行测试，预计结果将在未来几个月内公布。
即使疫苗与心肌炎之间的联系得到证实，刘说，疫苗的好处（可以很好地预防 COVID-19）大于风险，即使对于年轻人来说也是如此，因为他们患重症的风险通常较低。但 Mevorach 表示，鉴于以色列的 SARS-CoV-2 感染人数极少（昨天仅诊断出 15 例新病例），权衡利弊可能有所不同。他希望卫生部将是否为青少年接种疫苗的决定权留给他们的父母和医生。“目前，我们不再有紧急情况，”他说。
更新，2021 年 6 月 1 日，下午 4.55：已在这篇报道中添加了有关两例心肌炎死亡病例的文字；专家组表示对这些病例的调查尚无定论。
Israel reports link between rare cases of heart inflammation and COVID-19 vaccination in young men Study strengthens suspicions first announced in April, but most incidents are mild
1 JUN 2021BYGRETCHEN VOGEL, JENNIFER COUZIN-FRANKEL
Science's COVID-19 reporting is supported by the Heising-Simons Foundation.
The COVID-19 vaccine made by Pfizer and BioNTech appears to put young men at elevated risk of developing a heart muscle inflammation called myocarditis, researchers in Israel say. In a report submitted today to the Israeli Ministry of Health, they conclude that between one in 3000 and one in 6000 men ages 16 to 24 who received the vaccine developed the rare condition. But most cases were mild and resolved within a few weeks, which is typical for myocarditis. "I can't imagine it's going to be anything that would cause medical people to say we shouldn't vaccinate kids," says Douglas Diekema, a pediatrician and bioethicist at Seattle Children's Hospital.
Israeli health officials first flagged the issue in April, when they reported more than 60 cases, mostly in young men who had received their second dose of vaccine a few days earlier. Around the same time, the U.S. Department of Defense began to track 14 such cases. In mid-May, the U.S. Centers for Disease Control and Prevention said it, too, was reviewing myocarditis cases. Officials at the European Medicines Agency said on 28 May they had received 107 reports of myocarditis following the Pfizer-BioNTech vaccine, or about one in 175,000 doses administered. But relatively few people under age 30 have been vaccinated in Europe.
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The Israeli panel's findings come as Israel and many European countries are debating whether younger adolescents should be vaccinated against COVID-19. Israel has been vaccinating teenagers 16 and older since late January, and the Ministry of Health is scheduled to announce tomorrow whether vaccinations will be opened to children 12 and older. Other countries, including the United States and Canada, began vaccinating children 12 and older in mid-May.
"From a parent's perspective, this really comes down to risk perception, assessment of the data," says Diekema, who has studied risk-benefit trade-offs. Even if a link between myocarditis and the vaccine holds up, the condition is usually mild, requiring treatment only with anti-inflammatory drugs, whereas COVID-19 infection can also cause serious disease and long-term side effects, even in young people. As suspicion has percolated about a possible connection, "I don't know many physicians who are changing their minds about vaccinating their kids," Diekema says.
In Israel, which relied almost exclusively on the Pfizer-BioNTech vaccine in its early and fast vaccination drive, the Ministry of Health in January assembled a panel led by Dror Mevorach, head of internal medicine at the Hadassah University Medical Center, to investigate the issue. Mevorach tells Science he and his colleagues identified 110 myocarditis cases among 5 million people in Israel who had received two doses of the Pfizer-BioNTech vaccine in the month before their diagnosis. That translates to about one in 50,000 vaccine recipients, a number that isn't concerning given the background rate of myocarditis in the general population, where it is typically triggered by viral or bacterial infections, including COVID-19.
But the rate of myocarditis following vaccination among young men was higher. Ninety percent of the cases picked up in Israel appeared in men, and although myocarditis is normally more common among young men, the rate among those vaccinated was somewhere between five and 25 times the background rate, the report says. (Two cases of fatal myocarditis have also been reported in Israel, but the panel says investigations of those deaths were inconclusive; one patient may have had a more generalized inflammatory syndrome, and the other diagnosis was "not verified," the report says.)
The new analysis "is very suggestive of a causal nature," between the vaccine and myocarditis, Mevorach says. "I am convinced there is a relationship."
"It does suggest that this is, at least statistically, a real phenomenon," says Peter Liu, a cardiologist and chief scientific officer of the University of Ottawa Heart Institute. Diekema says it's important to investigate "even a hint of a signal," but cautions that "while this report is suggestive … it requires validation in other populations by other investigators before we can be certain the link exists." Other factors may be in play, Diekema says. Now that children are back to socializing and playing sports, his hospital's emergency room is "seeing more viral diseases than we've seen in a year," and as a result, "I would expect to see a little bump in myocarditis versus a year ago." Ideally, scientists should compare cohorts of vaccinated and unvaccinated youngsters at the same time, Diekema says, and he's heartened that such studies are now gearing up.
Myocarditis cases following the Moderna vaccine, which isn't in use in Israel, are also being investigated in the United States. It's not clear why the two vaccines, which both rely on messenger RNA (mRNA), might heighten the risk. One possibility is that the very high antibody levels that both generate in young people may also, in rare cases, lead to a sort of immune overreaction that inflames the heart. "There's no question these [vaccines] are extremely immune-generating," Liu says. Mevorach says he suspects the mRNA itself might be playing a role. The innate immune system recognizes RNA as part of the body's defense against microbes—including RNA viruses like SARS-CoV-2, he notes. "I think that actually the mRNA is a kind of natural adjuvant," which ramps up the immune response, he says.
Diekema says the medical community is now on alert for youngsters with chest pain and other symptoms soon after vaccination—allowing them to be quickly identified, treated, and reported to health departments. Mevorach agrees that awareness among vaccinees, their parents, and their doctors is important for prompt and effective treatment. He says he and his colleagues treated about 40 cases. Only a few needed corticosteroids, he said, and most have recovered fully.
One important question is whether delaying the second vaccine dose might reduce any potential risk. There may be an opportunity to find out: Several countries have stretched the interval between the two doses from the 3 weeks tested and recommended by Pfizer to 12 or even 16 weeks, because they want to give as many people as possible at least one shot. A drop in myocarditis cases among those whose second dose was delayed might show up in data in the months ahead. Lowering the dose in young people may also be worth considering, Liu says. Pfizer's and Moderna's vaccines are now being tested at lower doses in children under 12, with results expected in the coming months.
Even if the link between the shots and myocarditis firms up, Liu says the vaccine's benefit—being well-protected from COVID-19—outweighs the risks, even for young people, who are generally at lower risk of severe disease. But Mevorach says the trade-offs may be different in Israel, given its extremely low numbers of SARS-CoV-2 infections—just 15 new cases were diagnosed yesterday. He hopes the Ministry of Health will leave the decision on whether to vaccinate younger teens to their parents and doctors. "At the moment, we no longer have an emergency," he says.
Update, 1 June 2021, 4.55 PM: Text has been added to this story about two reported fatal cases of myocarditis; the expert panel said investigations of those cases were inconclusive.
